Shibata M A, Hirose M, Masuda A, Kato T, Mutai M, Ito N
First Department of Pathology, Nagoya City University Medical School, Japan.
Carcinogenesis. 1993 Jul;14(7):1265-9. doi: 10.1093/carcin/14.7.1265.
The long-term effects of butylated hydroxyanisole (BHA), in combination with various other chemicals on the development of forestomach lesions in rats were investigated. BHA is a synthetic antioxidant, and the other agents included the glutathione-depleting agent diethylmaleate (DEM), the anti-inflammatory drugs indomethacin (IM), dexamethazone (DEX), 6-aminocaproic acetate (6-ACA) and FOY (gabexate mesilate), and the vitamin all-trans-retinol acetate (RA). Concurrent treatment with BHA (1% in diet) and DEM, IM, DEX or FOY for 52 weeks inhibited development of forestomach epithelial hyperplasia as compared to BHA alone, while simultaneous treatment with RA enhanced hyperplastic development. However, the inhibition by DEX or FOY was only partial and in the DEX case, in particular, might have been due to weight loss. Since the most effective inhibitory influence on BHA-induced forestomach lesions exerted in this 1-year experiment was by DEM, a further 2-year experiment was conducted to confirm whether DEM actually can exert inhibitory effects on BHA (2% in diet)-induced forestomach carcinogenesis. The results demonstrated that induction of forestomach hyperplasias and papillomas by BHA was significantly reduced by combination treatment with DEM. Both multiplicity and incidence of forestomach papillomas were significantly decreased, while squamous cell carcinoma development showed a tendency for decrease only.
研究了丁基羟基茴香醚（BHA）与其他多种化学物质联合使用对大鼠前胃损伤发展的长期影响。BHA是一种合成抗氧化剂，其他试剂包括谷胱甘肽消耗剂马来酸二乙酯（DEM）、抗炎药物吲哚美辛（IM）、地塞米松（DEX）、6-氨基己酸醋酸盐（6-ACA）和FOY（甲磺酸加贝酯），以及维生素全反式视黄醇醋酸酯（RA）。与单独使用BHA相比，BHA（饮食中1%）与DEM、IM、DEX或FOY同时处理52周可抑制前胃上皮增生的发展，而与RA同时处理则增强增生发展。然而，DEX或FOY的抑制作用只是部分的，特别是DEX的情况，可能是由于体重减轻所致。由于在这个为期1年的实验中，对BHA诱导的前胃损伤最有效的抑制作用是由DEM产生的，因此进行了进一步的为期2年的实验，以确认DEM是否真的能对BHA（饮食中2%）诱导的前胃癌变产生抑制作用。结果表明，DEM联合处理可显著降低BHA诱导的前胃增生和乳头状瘤。前胃乳头状瘤的数量和发生率均显著降低，而鳞状细胞癌的发展仅显示出下降趋势。
